DNA DSB Repair Dynamics following Irradiation with Laser-Driven Protons at Ultra-High Dose Rates

Protontherapy has emerged as more effective in the treatment of certain tumors than photon based therapies. However, significant capital and operational costs make protontherapy less accessible. This has stimulated interest in alternative proton delivery approaches, and in this context the use of laser-based technologies for the generation of ultra-high dose rate ion beams has been proposed as a prospective route. A better understanding of the radiobiological effects at ultra-high dose-rates is important for any future clinical adoption of this technology. In this study, we irradiated human skin fibroblasts-AG01522B cells with laser-accelerated protons at a dose rate of 10 9 Gy/s, generated using the Gemini laser system at the Rutherford Appleton Laboratory, UK. We studied DNA double strand break (DSB) repair kinetics using the p53 binding protein-1(53BP1) foci formation assay and observed a close similarity in the 53BP1 foci repair kinetics in the cells irradiated with 225 kVp X-rays and ultra- high dose rate protons for the initial time points. At the microdosimetric scale, foci per cell per track values showed a good correlation between the laser and cyclotron-accelerated protons indicating similarity in the DNA DSB induction and repair, independent of the time duration over which the dose was delivered

A Study to derive distribution of carotid intima media thickness and to determine its COrrelation with cardiovascular Risk factors in asymptomatic nationwidE Indian population (SCORE-India)

Background: There is presently no data to describe normal distribution of carotid intima-media thickness (CIMT), an established measure of subclinical atherosclerosis, in Indian subjects. Methods: In this multi-centric study, 1229 subjects with age ≥30 years and no previous cardiovascular disease (CVD) underwent CVD risk factor assessment and CIMT measurement. Mean far wall common carotid artery IMT was measured on both sides and averaged. Results: Mean age of the subjects was 48.0 ± 12.0 years and 54.2% were men. CIMT measurement was feasible in 1157 subjects. Mean, median and 75th percentile values of CIMT for different age-groups were derived for men and women separately. There was a progressive increase in CIMT with increasing age (P < 0.001) and men had higher CIMT values than women (0.608 ± 0.12 mm vs. 0.579 ± 0.11 mm, P < 0.001). The CIMT values were also higher in diabetics (0.635 ± 0.10 mm) and hypertensives (0.624 ± 0.10 mm) as compared to non-diabetics (0.589 ± 0.12 mm, P < 0.001) and non-hypertensives (0.592 ± 0.12, P 0.02) respectively. Among continuous variables, age, systolic blood pressure and fasting blood glucose had strong to modest correlation with CIMT (Pearson's r 0.524, 0.282 and 0.192 respectively, all P values <0.001), whereas body mass index, diastolic blood pressure and serum triglycerides exhibited weak but still statistically significant relationship (Pearson's r 0.069, P 0.019; Pearson's r 0.065, P 0.026; and Pearson's r 0.094, P 0.001, respectively). Conclusions: This is the first study to provide age- and gender-specific distribution of CIMT in Indian subjects free from CVD. This information should help facilitate further research and clinical work involving CIMT in India